title: piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling.
abstract: The mammalian Phospholipase D MitoPLD facilitates mitochondrial fusion by generating the signaling lipid phosphatidic acid (PA). The Drosophila MitoPLD homolog Zucchini (Zuc), a proposed cytoplasmic nuclease, is required for piRNA generation, a critical event in germline development. We show that Zuc localizes to mitochondria and has MitoPLD-like activity. Conversely, MitoPLD(-/-) mice exhibit the meiotic arrest, DNA damage, and male sterility characteristic of mice lacking piRNAs. The primary function of MitoPLD seems to be the generation of mitochondrial-surface PA. This PA in turn recruits the phosphatase Lipin 1, which converts PA to diacylglycerol and promotes mitochondrial fission, suggesting a mechanism for mitochondrial morphology homeostasis. MitoPLD and Lipin 1 have opposing effects on mitochondria length and on intermitochondrial cement (nuage), a structure found between aggregated mitochondria that is implicated in piRNA generation. We propose that mitochondrial-surface PA generated by MitoPLD/Zuc recruits or activates nuage components critical for piRNA production.
authors.affiliation: Department of Pharmacology, Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794-5140, USA.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Huang
authors.forename: Qun
authors.initials: Q
authors.lastname: Gao
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Peng
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Choi
authors.forename: Krishna
authors.initials: K
authors.lastname: Sarma
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frohman
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004622:Embryo, Mammalian / Q000166:cytology; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010711:Phosphatidate Phosphatase; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D007527:Isoenzymes; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D010712:Phosphatidic Acids; D034741:RNA, Small Interfering; D017411:Ribonucleoproteins, Small Nuclear; C488681:Tdrd1 protein, mouse; D004722:Endoribonucleases; C521347:Zuc protein, Drosophila; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase; D010739:Phospholipase D